The mechanism by which ionizing radiation and reduced oxygen species damage DNA/genetic apparatus in vitro and in mammalian cells will be examined. DNA interstrand crosslinking and DNA-protein crosslinking induced in isolated chromatin by H2O2/Fe ions, H2O2 plus near UV light and ionizing radiation will be investigated. An attempt will be made to quantitatively compare DNA strand scission and DNA interstrand crosslinking in homogenous T7 DNA. The technique of high resolution mass spectrometry will be used to analyze for base modification induced in DNA. It appears that modified bases can be released from DNA more easily than unmodified bases. Mammalian cells will be examined for the presence of DNA strand scission, DNA-protein crosslinks, DNA interstrand crosslinking and modified bases after treatment with H2O2 plus near UV light.